Histological alterations in renal specimens as indicators of prognosis of IgA nephropathy.

A retrospective clinicopathological study of 66 patients with IgA nephropathy was undertaken to determine the prognostic significance of various renal histopathological alterations and clinical parameters. At the latest follow-up, after a period of 60 to 72 months following biopsy, 18 patients had serum creatinine concentration above 1.8 mg/dl. When the entire patients were evaluated as a whole, the extents of interstitial broadening and glomerular sclerosis were correlated significantly with the final status of renal function: proteinuria of more than 1.0 g per day and mildly impaired renal function at the time of biopsy were also associated with unfavourable outcome. However, when the patients with initially normal renal function, i.e. serum creatinine level below 1.2 mg/dl, were evaluated separately, the initial amount of proteinuria, but none of the other parameters, had a prognostic significance in the subsequent course of renal function. These findings suggest that proteinuria of more than 1.0 g per day as an early event often indicates the progression of IgA nephropathy, and lead to a postulation that renal histopathological changes become more significant prognostic indicators in the relatively advanced stage of the disease.     

Therapeutic approach of patients with IgA nephropathy

Immunoglobulin A nephropathy (IgAN) is the most commonly encountered primary glomerulonephritis and it usually follows an indolent clinical course. However, hypertensive patients with proteinuria and renal insufficiency at presentation and patients with severe histological involvement are at high risk to develop end stage renal failure. There is no consensus for the treatment of patients with IgA nephropathy. In general, patients with normal renal function, mild proteinuria (3 g/24 h) and in progressive disease despite treatment with ACE inhibitors. Fish oil might be an alternative to corticosteroids in cases with renal insufficiency and chronic histological lesions. Combinations of corticosteroids and cytotoxic drugs are saved for patients with IgA nephropathy and a rapidly progressive course.     

Renal survival rate of IgA nephropathy

In an attempt to identify prognostic indicators in IgA nephropathy, we evaluated the relationship between clinical and histological findings and changes in renal function in 81 patients with IgA nephropathy whose creatinine clearance was more than 80 ml/min at the time of renal biopsy. The incidence of patients whose creatinine clearance decreased to less than 60 ml/min during the follow-up period was calculated with the life table method to designate the renal survival rate. This rate was compared according to the clinical and histological findings at the time of renal biopsy. In conclusion, a statistically significant decrease in the renal survival rate was observed in patients with proteinuria of more than 1.0 g/day, hypertension, severe diffuse proliferative glomerulonephritis, diffuse proliferative glomerulonephritis with focal crescents and glomerular deposition of IgM and/or fibrinogen-related antigen.     

Immunoglobulin M and C1q mesangial labeling in IgA nephropathy

Colabeling with complement compont C1q or immunoglobulin M (IgM) is occasionally reported in biopsy specimens from patients with IgA nephropathy. The significance of this finding has been questioned. In 83 children and young adults with otherwise typical IgA nephropathy, 15 patients had more than trace mesangial labeling for IgM or C1q. Of these, 14 patients (93%) had greater than 1 + proteinuria at the time of biopsy. This was in marked distinction to the patients with no mesangial labeling for these reactants, only 15% of whom had greater than 1 + proteinuria. The children with IgM or C1q colabel did not differ from those lacking this finding in age at presentation, length of follow-up, or current renal function. In childhood IgA nephropathy, colabeling with IgM or C1q is seen frequently, probably is a function of heavy proteinuria at the time of biopsy, and does not contribute adversely to outcome.     

Clinicopathological features and the prognosis of IgA nephropathy in Japanese children on long-term observation

AIMS: Clinicopathological features were investigated to clarify the ultimate prognosis and prognostic indicators for patients with IgA nephropathy in Japanese children. METHODS: We evaluated the outcomes of 181 patients in whom IgA nephropathy was diagnosed before the age of 15 years since September 1979 and followed-up at least for three years with regard to clinical data at the onset of symptoms and renal histologic data. RESULTS: After mean follow-up of 7.3 years from onset, 91 patients of 181 (50.3%) were in clinical remission at the last examination, 24 (13.2%) had isolated hematuria, 59 (32.6%) had hematuria and proteinuria. Eighteen of 59 (9.9%) had proteinuria more than 1 g per 24 hours. Hypertension was observed in 12 cases and 7 (3.9%) developed end-stage renal disease. Except 7, no patient had reduced renal function and elevated serum creatinine at the final follow-up. Predicted renal survival rate from onset was 92.3% at 10 years and 89.1% at 20 years. In multivariable analysis, age at onset and chronic changes of tubulointerstitium were associated with poor outcome. CONCLUSIONS: Of 181 children with IgA nephropathy, 50% regressed, remaining 46% had hematuria and/or proteinuria and 4% of patients lapsed into end-stage renal disease. Our results indicate that childhood IgA nephropathy has a benign course and the risk for end-stage renal disease is lower than that of adults. Age at onset and tubulointerstitial lesions were the strong predictors of a progressive course of childhood IgA nephropathy.     

Repeat renal biopsy in children with IgA nephropathy

Serial renal biopsy findings in 61 children with IgA nephropathy were correlated with their clinical course. At the time of the second biopsy, 23 patients showed clinical remission defined as complete disappearance of proteinuria and hematuria with normal renal function while 38 had persistent urinary abnormalities with normal renal function at the second biopsy. There were no differences between the two groups with regard to initial clinical findings and pathologic findings of the initial renal biopsy. The second biopsy of patients with clinical remission showed improvement of the glomerular changes on light microscopy, disappearance or diminution of IgA deposits in the mesangium and decrease of electron-dense deposits, whereas the second biopsy of patients with persistent urinary abnormalities showed progression of glomerular changes on light microscopy, persistence of mesangial IgA deposits and persistence of electron-dense deposits. Our study results show the importance of repeat renal biopsy in children with IgA nephropathy with persistent urinary abnormalities, as a progression of glomerular changes is common in these patients. These observations suggest that the deposition of IgA in the mesangium may be responsible for the glomerular damage in children with IgA nephropathy.     

Specific controversies concerning the natural history of renal disease in pregnancy

Whether or not pregnancy adversely affects the natural course of underlying primary renal disease, and whether fetal outcome is influenced by the type of renal disease per se are controversial issues. We retrospectively analyzed the fetal and maternal outcome in 148 women with various, biopsy-proven histological types of primary chronic glomerulonephritis (GN), including IgA GN (52 patients), membranous GN ([MGN] 20 patients), membranoproliferative type 1 GN ([MPGN] 58 patients), focal and segmental glomerulosclerosis ([FSGS] 13 patients), and minimal change nephrotic syndrome ([MCNS] 22 patients), who were pregnant (with a total of 290 pregnancies) after the clinical onset of GN, and in 104 women with reflux nephropathy (with a total of 254 pregnancies). Fetal outcome was poor in the presence of uncontrolled hypertension, nephrotic range proteinuria, and/or impaired renal function at conception or early in gestation, whatever the type of renal disease. An accelerated, more rapid than expected, worsening of maternal renal function was observed in five GN patients of whom four (two IgA, two MPGN) had serum creatinine (Scr) levels greater than 160 mumol/L (1.8 mg/dL) early in gestation, and in five patients with reflux nephropathy whose Scr at conception ranged from 180 to 490 mumol/L (2.0 to 5.5 mg/dL).(ABSTRACT TRUNCATED AT 250 WORDS)     

IGA nephropathy: a retrospective evaluation of prognostic indices in 176 patients

One hundred and seventy-six patients with mesangial IgA nephropathy have been studied retrospectively. Mean follow up from apparent onset of the disease was 9.3 years and with follow up from the diagnostic renal biopsy of 4.6 years. Our aim was to evaluate the prognostic significance of sex, age and type of symptoms at onset. The degree of proteinuria, presence of hypertension or decreased renal function, histological lesions and IFL pattern at the time of the diagnostic renal biopsy were recorded. 17 of the patients developed End Stage Renal Failure (ESRF) during the study. According to the Logrank test (renal survival) and Cox stepwise proportional hazard model, severity of glomerular mesangial lesions and degree of proteinuria are the most important indicators of a poor prognosis. The significance of all other parameters disappear after correction for histological lesions and degree of proteinuria. Our conclusion is that a semiquantitative light microscopical examination is an excellent prognostic index in IgA nephropathy, as is a simple determination of protein excretion in the urine.     

肾功能不全的IgA肾病患者临床表现与病理特点分析

目的分析肾脏活体组织检查（简称：肾活检）时肾功能异常的IgA肾病患者的临床表现与病理特点。方法选择我院经肾活检确诊的190例IgA肾病患者为研究对象,以其患者血肌酐（SCr）130μmol／L为界分为2组：肾功能正常组（SCr〈130μmol／L）128例和肾功能异常组（SCr≥130μmol／L）62例。同时对其肾脏病理进行半定量评分,比较2组患者的临床病理特点,并且通过回归分析与其肾功损害相关的因素。结果与肾功能正常组相比,肾功能异常组男性比例明显增高（72．6％1;L28．9％,P〈0．01）,年龄更大[（34±10）岁比（30±9）岁,P〈0．01],病程更短[（11±17）]个月比（20±41）个月],同时收缩压更高[（141±19）比（123±17）mmHg,P〈0．01],24h尿蛋白定量增多[（3．31±2．70）g比（2．25±2．19）g,P〈0．01]。同时其患者肾脏病理反映慢性病变的指数均明显增高。多因素分析还显示,与肾活检时肾功能异常密切相关的危险因素包括男性,年龄增大,收缩压增高,24h尿蛋白定量增多,以及肾小管萎缩和间质纤维化指数增高。结论肾活检时肾功能异常的IgA。肾病患者临床表现和肾脏病理改变均明显加重,肾小管萎缩和间质纤维化指数增高与IgA肾病患者肾活检时肾功能异常独立相关。     

Nephrotic-range proteinuria in a patient with a renal allograft treated with sorafenib for metastatic renal-cell carcinoma

A 51-year-old man with immunoglobulin A (IgA) nephropathy developed metastatic renal-cell carcinoma of his native right kidney, 3.5 years post kidney transplant. At that time renal function was stable with the presence of only mild proteinuria. Shortly after chemotherapy with sorafenib [anti-vascular endothelial growth factor (VEGF)] was initiated, progressive renal impairment, hypertension, and nephrotic-range proteinuria developed. Allograft biopsy showed extensive IgA nephropathy. After withdrawal of the anti-VEGF therapy, however, renal function and blood pressure improved, and proteinuria diminished. Based on the clinical course and histopathological findings we hypothesize that sorafenib may induce nephrotic-range proteinuria and renal impairment, possibly through anti-VEGF-mediated effects on the progression of IgA nephropathy.     

Clinicopathologic correlations in a series of 143 patients with IgA glomerulonephritis

In an unselected series of patients with IgA glomerulonephritis, old age, high blood pressure, and high urinary protein excretion at the time of renal biopsy were found to correlate with impaired renal function, whereas sex, estimated duration of the disease, or high serum IgA levels did not. The following clinical features were favorable prognostic signs: asymptomatic proteinuria, macroscopic hematuria, and isolated microscopic hematuria. The degree of diffuse mesangial alteration and the presence of segmental glomerular lesions correlated clearly with the subsequent clinical outcome. Vascular lesions, i.e. arteriosclerosis and renal vascular deposition of C3, were most often present in patients with severe glomerulopathy. The presence of electron-dense deposits in glomerular capillary walls was also an unfavorable prognostic finding. Renal biopsy findings of interstitial infiltrates of inflammatory cells and IgA distributed along glomerular capillary walls were usually associated with extrarenal manifestations of the disease.     

Macroscopic hematuria and proteinuria preceding renal IgA deposition in patients with IgA nephropathy

Although the clinical onset of IgA nephropathy is frequently impossible to define, macroscopic hematuria apparently heralds the onset of the disease in some patients. We describe the clinical course and renal histologic findings of four adults with IgA nephropathy who were diagnosed by the characteristic immunohistologic features in a second renal biopsy specimen. IgA was not detected in the initial renal biopsy specimens obtained 9 months to 4 years earlier. The first renal biopsy had been performed to evaluate macroscopic hematuria (recurrent in three patients), accompanied by pathologic proteinuria in two patients. Our observations suggest that the pathognomonic immunohistologic findings of IgA nephropathy may follow the clinical onset and raise questions about the presumed pathogenetic role of IgA in the early stages of this disease.     

Multivariate analysis of prognostic factors and effect of treatment in patients with IgA nephropathy

BACKGROUND: Although the clinical and histological prognostic factors of IgA nephropathy have been investigated in detail, the value of treatment in terms of renal outcome is not well understood. METHODS: The authors examined data from 237 patients with IgA nephropathy (age 31.4+/-13.5 years, mean+/-SD) who had been followed-up for at least six months (follow-up periods, 62.3+/-45.5 months). The authors initially tested the significance of prognostic factors (age, sex, systolic blood pressure, proteinuria, serum creatinine, and histological severity) and treatment strategies (steroid therapy, renin-angiotensin system inhibitors and tonsillectomy) on renal outcome with univariate analysis, then evaluated the findings using the Cox proportional hazards model. RESULTS: Univariate and multivariate analyses showed that among the prognostic variables, a high level of serum creatinine at renal biopsy, large amounts of proteinuria, and extensive histological injury were significant risk factors for end-stage renal failure. Kaplan-Meier analysis showed that the renal survival rates associated with these factors were significantly poorer depending on their severity. Univariate analysis revealed that tonsillectomy was the only significant treatment that contributes to the maintenance of renal survival. Moreover, urinary abnormalities disappeared at a significantly higher frequency when patients were treated by tonsillectomy. The Cox proportional hazards model showed that steroid therapy independently contributed to improve renal prognosis in addition to tonsillectomy, and the hazard ratios were 0.26 (95% CI, 0.07 to 0.93) and 0.37 (95% CI, 0.14 to 0.99), respectively. CONCLUSION: Steroid therapy and tonsillectomy can independently improve renal outcome in patients with IgA nephropathy.     

Steroid therapy in IgA nephropathy: a retrospective study in heavy proteinuric cases

29 patients with IgA nephropathy whose proteinuria persisted at a level of 2.0 g/day or more and who received prednisolone treatment for 1-3 years were retrospectively evaluated on their clinical courses. 13 of 14 patients with renal dysfunction of less than 70 ml/min in initial creatinine clearance (Ccr) values subsequently entered a progressive course during a follow-up period of 47 months, leading to end-stage renal failure in 8 cases. On the other hand, only 1 of the other 15 patients with preserved renal function of 70 ml/min or more ended up with end-stage renal failure during a follow-up period of 74 months, although 7 underwent a progressive course. Three patients in the latter group experienced a prominent reduction in proteinuria to less than 1.0 g/day and maintained renal function. Meanwhile, the steroid group of moderate proteinuric patients with a creatinine clearance greater than 70 ml/min had a benign course, while the nonsteroid group had an unfavorable one. These results suggest that steroid therapy in IgA nephropathy may be able to stabilize a progressive course, especially in the early stage of the disease, although, because they come from an uncontrolled study, a definite conclusion cannot be drawn.     

Prognostic indicators of IgA nephropathy in the Chinese--clinical and pathological perspectives.

BACKGROUND: IgA nephropathy is the most common primary glomerulonephritis in the world. Up to 30% of patients can progress to end-stage renal disease (ESRD) in 10 years. METHODS: We studied 168 Chinese patients with IgA nephropathy followed for an average of 7.4 years in our hospital and tried to identify the clinical and pathological data that were associated with the prognosis of the disease. Clinical features at the time of renal biopsy were reviewed. Severity of histological involvement was scored semi-quantitatively as grade 1-3. RESULTS: There was a female preponderance in our cohort of patients (male:female ratio 1:1.5). The average age at biopsy was 32.9+/-10.0 years. Forty-seven of the 168 patients (28.0%) were hypertensive and 47 of 136 patients (34.6%) had a family history of hypertension. A high histological grade of IgA nephropathy was associated with hypertension at presentation, family history of hypertension, a higher serum creatinine, total cholesterol and 24-h urine protein excretion, and a lower serum albumin level. During the follow-up period, four patients died and another 24 progressed to ESRD. The renal survival was 92.0% at 1 year, 87.5% at 5 years and 81.8% at 10 years. With univariate analysis, hypertension at presentation, family history of hypertension, renal impairment at presentation (plasma creatinine >120 micromol/l), high cholesterol, proteinuria >1 g/day and high histological grading were associated with poor prognosis. With multivariate analysis, hypertension at presentation, family history of hypertension, renal impairment at presentation, proteinuria >1 g/day and histological grading were independent predictors of renal survival. The relative risks of renal failure for patients were 9.60 (95% confidence interval 4.02-22.92) with hypertension, 1.56 (1.16-2.02) with a family history of hypertension, 15.38 (6.40-36.93) with renal impairment and 5.93 (3.07-11.46) with every increase of one histological grade. Male patients did not show a more adverse outcome compared with females. CONCLUSIONS: Our results suggest that renal biopsy remains useful, even in clinically trivial disease, because of its distinct value in prognosis and risk stratification. The long-term prognosis of IgA nephropathy in Chinese patients is guarded. The prognostic importance of family history of hypertension has not been widely recognized and requires further study.     

Prognostic indicators in childhood IgA nephropathy.

A number of clinical, laboratory and pathologic parameters were assessed for their prognostic significance in 200 children aged less than 15 years with IgA nephropathy, who had shown normal renal function at the time of initial biopsy and were followed for more than 2 years thereafter. After a mean follow-up period of 5.0 years from the initial biopsy, 93 patients had no demonstrable abnormality, 76 had minor urinary abnormalities, 21 had persistent heavy proteinuria and 10 had developed chronic renal impairment. A poor outcome was found to be correlated with heavy proteinuria at biopsy, diffuse mesangial proliferation, a high proportion of glomeruli showing sclerosis, crescents or capsular adhesions, the presence of moderate or severe tubulointerstitial changes, and the presence of subepithelial electron-dense deposits and lysis of the glomerular basement membrane by electron microscopy. The percentage of glomeruli displaying crescents, sclerosis and adhesions appeared to be the most reliable prognostic indicator. Nine of the 27 patients (33%) in whom greater than or equal to 30% of glomeruli showed crescents, sclerosis and adhesions developed chronic renal impairment, and only 14% of these patients had normal urine at follow-up. In contrast, only 1 of the 173 patients in whom less than 30% of glomeruli showed such lesions developed chronic renal impairment (p less than 0.001) and 51% of these patients showed complete remission at follow-up (p less than 0.001). These results demonstrate that an accurate prediction of the outcome based on the initial renal biopsy findings is possible early in the course of children with IgA nephropathy.     

Therapy of IgA nephropathy with mycophenolate mofetil--report of 3 cases

Mycophenolate mofetil is an immunosuppressive agent in transplantation which inhibits the purin neogenesis. Proliferating lymphocytes are suppressed and antibody production is decreased. Many cases of successful therapy in different kidney diseases are reported, such as diffuse proliferative lupus nephritis, pauci-immune necrotizing glomerulonephritis, focal segmental glomerular sclerosis and IgA nephropathy. We report 3 patients with IgA nephropathy who were treated with mycophenolate mofetil for more than 1 year. In all patients, proteinuria decreased significantly and the renal function remained stable. In 2 patients, kidney biopsy was repeated after 12 months and 18 months, respectively. There were no histological signs of progression of the disease. Two patients developed infections during treatment. One patient had a pneumonia, and a second patient an infection with varizella zoster. Based on our data, mycophenolate mofetil can be a potential treatment of IgA nephropathy. Further controlled studys are warranted to investigate the role of mycophenolate mofetil in IgA nephropathy.     

Superimposition of poststreptococcal acute glomerulonephritis on the course of IgA nephropathy

A 17-year-old male with poststreptococcal acute glomerulonephritis (PSAGN) superimposed on the course of IgA nephropathy is presented. The histological findings of the first renal biopsy showed mild IgA nephropathy with a mesangial deposition of IgA and C3. Eighteen months later, acute nephritic syndrome with hypocomplementemia and rising antihyaluronidase titer occurred 10 days following the onset of an upper respiratory infection. The second renal biopsy revealed severe diffuse endocapillary proliferative and exudative glomerulonephritis with cellular crescents in 70% of the glomeruli. Immunofluorescence showed granular staining of C3 alone along the capillary walls. The pre-existing IgA deposits had disappeared. Typical 'humps' were observed by electron microscopy. The symptoms were gradually resolved by intensive steroid and anticoagulant therapy. Five months after the episode of acute nephritic syndrome, the patient was clear of symptoms except for mild proteinuria and hematuria. The third renal biopsy at that time showed morphologic changes similar to those of the first renal biopsy with mild mesangial IgA deposits.     

少量蛋白尿IgA肾病临床研究现状

少量蛋白尿IgA肾病(24 h尿蛋白<1 g)的患者既往认为长期预后良好,且肾活检比例低,普遍未予积极有效的治疗。近年来陆续有研究表明,少量蛋白尿IgA肾病患者长期预后并不乐观,因此需提高对少量蛋白尿IgA肾病临床、病理、治疗及预后的认识及理解。本文将对少量蛋白尿IgA肾病临床表现、肾脏病理、治疗及预后4个方面予以综述。     

Analysis of clinical and pathological features of HIV associated renal disease

Objective To describe the presentation, pathology, and outcome of biopsy proved renal disease in HIV infected patients. Methods This retrospective study included all HIV infected patients who underwent renal biopsy during the course of their clinical care at PUMC hospital from 2002 to 2012. The pathology and clinical information were abstracted from each patient’s clinical record. Results Eight HIV infected patients had biopsy confirmed renal disease. The commonest presentation was proteinuria in eight patients, and microscopic hematuria in six patients. Two patients had serum creatinine levels abnormal. Renal pathologies included IgA nephropathy in four patients, and lupus-like nephropathy, non-specific focal segmental glomerulosclerosis, membranous nephropathy and Henoch-Schonlein purpura nephritis in one patient each. All 8 patients received highly active antiretroviral treatment (HAART). Urinary protein was decreased significantly in one of them. Another was relieved with ACEI/ARB in addition to HAART. Corticosteroid was given to the other 6 patients. Among them, two got remission. one presented no reaction and was given cyclosporine. One, whose urinary protein didn't decrease with ACEI/ARB, received corticosteroid and needed further observation. One had continued aggravation of the renal disease. One case died of AIDS. One case companied with IgA nephropathy whose proteinuria recurrence was considered having association with tenofovir renal toxicity relieved after adjustment of HAART. Conclusions Classical HIVAN is uncommon in Chinese HIV infected population, a variety of other pathologies were seen in HIV infected patients, renal biopsy can help confirm the diagnosis. In HIV infected patients with evidence of nephropathy should be treated with HAART at diagnosis. Addition of prednisone should be considered if HAART alone does not result in improvement of renal disease.